NFATc2 Enhances Tumor-initiating Phenotypes Through the NFATc2/SOX2/ALDH Axis in Lung Adenocarcinoma

Overview

Journal Elife

Specialty Biology

Date 2017 Jul 25

PMID 28737489

Citations 28

Authors

Zhi-Jie Xiao

Jing Liu

Si-Qi Wang

Yun Zhu

Xu-Yuan Gao

Vicky Pui-Chi Tin

Jing Qin

Jun-Wen Wang

Maria Pik Wong

Affiliations

Soon will be listed here.

Abstract

Tumor-initiating cells (TIC) are dynamic cancer cell subsets that display enhanced tumor functions and resilience to treatment but the mechanism of TIC induction or maintenance in lung cancer is not fully understood. In this study, we show the calcium pathway transcription factor NFATc2 is a novel regulator of lung TIC phenotypes, including tumorspheres, cell motility, tumorigenesis, as well as in vitro and in vivo responses to chemotherapy and targeted therapy. In human lung cancers, high NFATc2 expression predicted poor tumor differentiation, adverse recurrence-free and cancer-specific overall survivals. Mechanistic investigations identified NFATc2 response elements in the 3' enhancer region of , and NFATc2/SOX2 coupling upregulates ALDH1A1 by binding to its 5' enhancer. Through this axis, oxidative stress induced by cancer drug treatment is attenuated, leading to increased resistance in a mutation-independent manner. Targeting this axis provides a novel approach for the long-term treatment of lung cancer through TIC elimination.

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